A cytokine study in children and adolescents with Tourette's disorder

Background

While immune system dysregulation has been postulated to play a role in Tourette's disorder (TD), most research has focused on the hypothesis of an autoimmune process similar to rheumatic fever. This study examined the potential role of cytokines, modulators of the immune system. We hypothesized that children with TD would have increased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β and IL-6, and decreased IL-2. We also explored whether comorbid obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients.

Method

Thirty-two children and adolescents with TD (27 males, ages 7–18 years), 17 with comorbid OCD (14 males), and 16 healthy comparison subjects (7 males, ages 9–19), were enrolled. Plasma cytokines were examined using an enzyme-linked immunosorbent assay. The Mann–Whitney and binary logistic regression tests were used to compare the groups.

Results

Only patients with comorbid OCD (TD+OCD; n = 17) had significantly elevated IL-12 plasma levels compared to controls (2.73 ± 5.12 pg/ml vs. 0.55 ± 0.88 pg/ml, rank statistic = 222.5; p < 0.04). IL-2 was significantly higher in the TD+OCD subgroup compared to the non-OCD TD subgroup (0.74 ± 0.29 pg/ml vs. 0.49 ± 0.24 pg/ml, rank statistics = 108.5; p < 0.03). There were no other significant cytokine differences between groups.

Conclusions

Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD−OCD subgroup. Larger studies with medication-free patients should follow.     

Effectiveness of home rehabilitation program for ischemic stroke upon disability and quality of life: a randomized controlled trial

Background

To develop and examine the effectiveness of individual 6-month home rehabilitation program in ischemic stroke patients upon disability and quality of life at 2 years.

Methods

This is a prospective randomized controlled trial (RCT) in 60 patients with recent ischemic stroke. They were randomly assigned to receive either home rehabilitation program once a month for 6 months with audiovisual materials (intervention group) or usual care (control group). We collected outcome data after discharge from the hospital until 2 years. The Barthel index (BI), the modified Rankin Scale (mRS) and utility index (EQ-5D) were measured for function, disability and quality of life respectively.

Results

At 2 years, the BI was significantly improved in the intervention group more than the control group: 97.2 ± 2.8 vs. 76.4 ± 9.4, p < 0.001. The good outcome, defined as BI 95–100, or mRS 0 or 1. For BI, there were 29 patients (96.7%) in intervention group vs 12 patients (42.9%) in usual care group (95% CI, 42.0, 85.0, p = 0.03). For mRS, there were 28 patients (93.3%) in intervention group vs 9 patients (32.1%) in usual care group (95% CI, 38.2, 87.0, p = 0.02). Number needed to treat for good outcome in mRS was 2.0 (95% CI: 1.0, 1.3). The mean (SD) of utility index in intervention group and control group were 0.9 ± 0.02 and 0.7 ± 0.04 respectively (p = 0.03). There was no significant interaction in baseline characteristics and treatment outcome.

Conclusions

Early home rehabilitation program in the first 6 months period after ischemic stroke leads to more rapid improvement in function, reducing disability and increase quality of life than usual care.     

Comparing efficacy and side effects of a weekly intramuscular biogeneric/biosimilar interferon beta-1a with Avonex in relapsing remitting multiple sclerosis: a double blind randomized clinical trial

Objective

We compared the efficacy and safety of two biosimilar forms of interferon beta-1a in the treatment of multiple sclerosis: Avonex (Biogen Idec, USA) and CinnoVex (CinnaGen, Iran).

Methods

In a double blind randomized clinical trial study 84 patients with relapsing remitting multiple sclerosis (RRMS) with Expanded Disability Status Scale (EDSS) score of 0–5.5 were randomly allocated to two groups of 42 subjects.

Results

Twenty-four patients lost to follow-up. Finally, 31 patients (mean ± SD of age = 33.7 ± 7.0; 7 males and 24 females) in the Avonex and 29 patients (mean ± SD of age = 32.2 ± 9.2; 8 males and 21 females) in the CinnoVex group completed full 24 months of study period. Decrease in EDSS was 1.05 ± 0.24, p = 0.62 in the Avonex and 0.16 ± 0.88, p = 1.0 in the CinnoVex group after 12 months and 0.27 ± 1.05, p = 0.46 in the Avonex and 0.16 ± 1.06, p = 1.0 in the CinnoVex group after 24 months. There was no statistically significant difference in attack number between two groups (1.0 ± 1.2 in Avonex and 1.2 ± 1.3 in CinnoVex; p = 0.46). Volume of T2-weighted lesions on MRI showed a progressive significant increase in the 12th month (28056 ± 23693) in Avonex treated patients compared with first image (16353 ± 11172) (p = 0.01). But number of gadolinium-enhancing lesions in CinnoVex showed statistically significant decrease after 12 months (0.08 ± 0.28 vs. 1.00 ± 1.22; p = 0.03). However, there were no significant differences between groups after 24 months. There were no significant differences between 2 groups regarding frequency and duration of most considerable side effects, as well. Neutralizing antibodies were not positive in any patients.

Conclusion

CinnoVex can be used as a safe and effective alternative to Avonex in treatment of RRMS.     

Surgical treatment of unruptured intracranial aneurysms in a low-volume hospital--outcome and review of literature

Background

The aim of this study was to evaluate surgical outcome of unruptured intracranial aneurysms (UIAs) in a low-volume hospital and compare the results with the recent literature.

Methods

A retrospective review of all consecutive craniotomies for UIA from July 1999 through June 2009 was performed. Morbidity was defined as modified Rankin Scale (mRS) ≥ 3 and evaluated six weeks after surgery. Cognitive function was evaluated at rehabilitation-to-home discharge. A PubMed database search (2001–2011) seeking retrospective, single-center studies reporting on surgical outcome of UIAs was performed.

Results

There were 47 procedures performed in 42 patients to treat 50 UIAs (mean of 5 annual craniotomies). The mean age was 54.7 ± 12.1 years and mean aneurysm size was 7.6 ± 4.0 mm. Favorable outcome (mRS 0–2) at six weeks after surgery was achieved in 45 of 47 procedures (95.7%). Aneurysm size ≥ 12 mm was statistically significant related to adverse outcome defined as mRS change ≥ 1 (71% vs. 29%; p = 0.018). Five patients (10.6%) with favorable neurological outcome (mRS 2) presented with cognitive impairment at rehabilitation-to-home discharge. There was no significant difference in overall morbidity and mortality comparing low- and high-volume hospitals (4.0% vs. 4.8%; p = 0.85).

Conclusions

Low-volume hospitals may achieve good results for surgical treatment of UIAs. The results indicate that defining numeric operative volume thresholds is not feasible to guide centralization of aneurysm treatment.     

Prediction of infarct growth and neurologic deterioration in patients with positive perfusion-diffusion mismatch

Background

To assess the value of baseline clinical severity and perfusion–diffusion mismatch as predictors for further infarct growth and clinical outcome.

Methods

Patients with acute ischemic stroke and initial perfusion–diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined.

Results

Fifty-two patients (mean age 68.3 ± 12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p = 0.02). Initial stroke severity, but not TTP and CBV mismatch (p = 0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration (p = 0.001).

Conclusions

In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.     

Mismatch negativity and low frequency oscillations in schizophrenia families

Objective

Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members.

Methods

We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits.

Results

We found that (1) MMN was reduced in patients (p < 0.001) and SSP subjects (p = 0.047) but not in relatives (p = 0.42); (2) there were augmented 1–20 Hz oscillations in patients (p = 0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR² = 21.4–23.9%, all p < 0.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h² = 0.56, p = 0.002) and theta-alpha (h² = 0.55, p = 0.004) were heritable traits.

Conclusions

Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm.

Significance

The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.     

Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings

Objective

To determine Red Blood Cell (RBC) antioxidant enzyme activities and plasma Thiobarbituric Acid Reactive Substances (TBARS) in clinically stable patients with schizophrenia and their unaffected siblings.

Methods

A case-control study carried out on three groups: 60 schizophrenic patients treated with neuroleptics, 33 of their unaffected siblings and 30 healthy controls with no family psychiatric history. Biological markers were measured on fasting patients after a period of tobacco abstinence: RBC antioxidant enzyme activities – superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) – by spectrophotometry and plasma levels of TBARS by spectrofluorimetry.

Results

RBC SOD and CAT activities were significantly lower in schizophrenic patients and their unaffected siblings compared to the control group (P < 0.001). Schizophrenic patients also had significantly lower RBC GSH-Px activity than controls (P = 0.03), whereas their unaffected siblings had significantly higher RBC GSH-Px activity than controls (P = 0.04). Plasma TBARS were higher in schizophrenic patients than their unaffected siblings: 2.1 ± 0.8 μmol/l vs. 1.7 ± 0.6 μmol/l (P = 0.06).

Conclusions

Our results showed a decrease in antioxidant enzyme activities and an increase in lipid peroxidation confirming the existence of oxidative stress in schizophrenic patients treated with neuroleptics. Additionally, this suggests that the increase in GSH-Px activity in unaffected siblings would be a protective mechanism against oxidative stress and damage. Other studies are necessary to confirm these findings.     

Comparison of two methods for the detection of oligoclonal bands in a large number of clinically isolated syndrome and multiple sclerosis patients

Objective

A novel oligoclonal band (OB) assay which consists of isoelectric focusing (IEF) and IgG immunodetection by alkaline phosphatase-labeled anti IgG antibody was reported to be very sensitive. It also accurately predicted conversion to MS in patients with CIS. The aim of our study was to compare sensitivity of a novel and the standard procedure with peroxidase immunodetection in a large number of CIS and MS patients.

Methods

OB were determined in serum and CSF samples in 161 patients (104 females), 47 with CIS and 114 with MS with median age 38 years (range 19–68) using both methods.

Results

Eighty-three percent of patients had CSF OB with the standard and 89% with the novel method. Median number of OB was 5 (range 0–17) with the peroxidase and 8 (range 0–18) with the alkaline phosphatase method; p = 0.001. Twenty-one percent of patients had ≥10 OB with the standard and 37% with the novel method of the detection; p = 0.021. Subjective impression of band clarity showed that 20% of patients had sharper and stronger bands when the peroxidase and 65% when the alkaline phosphatase method was used; p < 0.0001.

Conclusion

The alkaline phosphatase method is more sensitive than the peroxidase method and at the same time cheaper, easy to perform and less time consuming.     

Bandpass filter settings differentially affect measurement of P50 sensory gating in children and adults

Objective

This study investigated the effect of four different bandpass filter settings on measures of the P50 component and the signal-to-noise ratios (SNR) of averaged ERPs obtained from a sensory gating paradigm employing paired-click stimuli.

Methods

Participants were adults (n = 18) 20–55 years old and children (n = 25) 5–10 years old who were free of neurological disorders.

Results

Results show that the filter settings (0.23–75 Hz, 10–50 Hz, 10–75 Hz, and 10–200 Hz) differentially affected the P50 amplitude, noise power and SNR measures of the conditioning and test clicks, and P50 T/C ratios.

Conclusions

The 10–50 Hz filter setting may be optimal in studies that include only adults as these settings resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD) for the ratio, and the highest SNRs. The 10–200 Hz filter may be the best for studying young children as this setting had the smallest mean and SD of P50 T/C ratios for these participants.

Significance

In studies that include both adults and children investigators are advised to use the 10–200 Hz filter setting because the smaller variability of sensory gating in the child group helps ensure better homogeneity of variance measures between the groups.     

Age-related changes in the control of perturbation-evoked and voluntary arm movements

Objective

This study examined how handrail location predictability affects perturbation-evoked arm responses in young and older adults and whether age-related changes in perturbation-evoked arm responses are specific to mechanisms associated with reactive postural control.

Methods

Young and older adults reached for a handrail in response to a support surface translation (perturbation-evoked) or to a visual cue (voluntary). For both movement tasks, the handrail location was made predictable or unpredictable to the participant. Electromyographic (EMG) activity and kinematics of the reaching arm were recorded to quantify the arm response.

Results

Posterior deltoid EMG activity during perturbation-evoked and voluntary movements were delayed by 15–74 ms (p < 0.001) and 16% smaller (p = 0.024) when the handrail was in an unpredictable compared to a predictable location. While ageing resulted in a 12–16 ms delayed initiation of EMG activity during perturbation-evoked reaching (p = 0.003), the effects of handrail predictability and movement task did not interact with age.

Conclusions

Age-related differences in perturbation-evoked arm responses are independent of both handrail location predictability and movement task.

Significance

Age-related differences in perturbation-evoked arm responses cannot be solely attributed to declines in reactive postural control. Rather, ageing leads to a deterioration of neural mechanisms common to both perturbation-evoked and voluntary arm movements.     

Anhedonia in Japanese patients with Parkinson's disease: analysis using the Snaith-Hamilton Pleasure Scale

Background

Anhedonia, a lowered ability to experience physical or social pleasure, has recently been recognized as a non-motor symptom of Parkinson's disease.

Objective

To identify the frequency of anhedonia and the factors influencing hedonic tone in Japanese patients with Parkinson's disease.

Patients and methods

We recruited 86 consecutive outpatients with a clinical diagnosis of PD attending two Japanese hospitals (one university hospital and one community hospital) in February 2010. We used the self-rating Snaith–Hamilton Pleasure Scale (SHAPS) translated into Japanese language from the original English version to assess and quantify hedonic tone as a subjectively experienced phenomenon. We studied the association of anhedonia with the variables age, age at onset, gender, disease duration, disease severity and antiparkinsonian drugs.

Results

Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was 72.01 ± 9.07 (49–89) years, with mean age at onset of 64.93 ± 11.42 (31–88) years. Mean disease duration was 7.20 ± 5.54 (1–23) years. The mean Hoehn and Yahr scale was 2.76 ± 0.78. The mean SHAPS score of the total sample was 1.19 ± 1.86. The SHAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia. The mean SHAPS score was lower in patients taking pramipexole (0.58 ± 0.97) than in patients not taking pramipexole (1.57 ± 2.16). Multiple linear regression analysis identified pramipexole as a significant negative influencing factor on the SHAPS score, while disease severity and entacapone treatment were identified as positive influencing factors. The age, onset age, gender, disease duration, and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents and droxidopa did not significantly affect the SHAPS score.

Conclusion

Anhedonia is not rare non-motor symptom in Japanese patients with Parkinson's disease. This study suggests an anti-anhedonic property of pramipexole.     

Malignant glioma grade 3 and 4: How relevant is timing of radiotherapy?

Aims and background

The aim of this study is to determine prognostic factors that influence further outcome in patients with glioma.

Methods

Between 01/2002 and 08/2008, 153 patients with malignant gliomas of WHO-grade 3 or 4 who were treated with external beam radiotherapy with or without chemotherapy.

Results

In univariate analysis, following factors were ascertained as statistically significant prognostic parameters: grade (p = 0.000), time between operation and radiotherapy >24 days (p = 0.044) for progression-free survival; grade (p = 0.000), age < 58 years (p = 0.001), extent of surgery (p = 0.011), time between operation and radiotherapy >24 days (p = 0.009), overall treatment time >68 days (p = 0.003), use of chemotherapy (p = 0.015) for overall survival. A longer time period between resection and start of radiotherapy showed to be associated with improved outcome. After multivariate analysis, only grade (p = 0.000) remained a statistically significant factor for progression-free and grade (p = 0.000) and use of chemotherapy (p = 0.031) for overall survival.

Conclusions

We were able to recognize grade and use of chemotherapy as statistically significant prognostic determinants, but not time intervals or overall treatment time.     

Platelet poor plasma serotonin level in delinquent adolescents diagnosed with conduct disorder

Objective

Accumulating data indicate the involvement of the serotonergic system in adolescent aggression. The aim of this study was to examine the platelet-poor plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with conduct disorder (CD) in comparison with normal controls.

Method

PPP 5-HT levels were measured in 16 male delinquent CD adolescents from a correctional facility and in 14 normal male adolescent controls. Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS).

Results

Delinquent CD adolescents had higher PPP 5-HT levels (about 3-fold) than the normal controls (27.68 ± 32.29 vs. 7.76 ± 4.23 ng/ml, respectively, p = 0.027). In the delinquent CD adolescents a significant correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive scores (r = 0.68, p = 0.0034 and r = 0.59, p = 0.016, respectively).

Conclusions

Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT neurotransmission may have a role in the symptomatology and treatment of severe adolescent CD.     

Effect of concentration and mode of intrathecal baclofen administration on soleus H-reflex in patients with muscle hypertonia

Objectives

Assess spinal reflex excitability after increasing intrathecal baclofen (ITB) flow by manipulation of drug concentration and mode of administration.

Methods

The effect of concentration was assessed by comparing changes in H-reflex (H/M ratio) 1–6 h after a 50 μg ITB bolus at 50 μg/ml concentration administered manually via lumbar puncture (LP, duration 1–2 min, n = 27) to a 50 μg bolus at 500 μg/ml concentration programmed through the pump and delivered via intrathecal catheter (IC, duration 10 min) above simple continuous dose (25–100 μg/day, n = 16). The effect of mode of administration was assessed by comparing peak changes in H/M ratio after 50 μg IC bolus above simple continuous dose (complex continuous mode, n = 27) to simple continuous mode only (n = 22) at equivalent daily doses (75–150 μg/day).

Results

H/M decrease was faster and overall greater after LP than IC bolus (mean 1-h 77% vs. 63%, p = 0.012; 1–6 h 91% vs. 82%, p < 0.001, respectively). H/M ratio also decreased significantly more with complex (91%) than simple continuous mode of administration (78%, p = 0.025).

Conclusions

Lower ITB concentration and complex continuous mode of administration lead to greater decrease in H/M ratio.

Significance

Decreased spinal reflex excitability after adjustment of drug and pump parameters to increase ITB flow may result in better clinical response.     

Short latency afferent inhibition associated with cortical compression and memory impairment in patients with chronic subdural hematoma

Objective

To evaluate the cortical excitability in patients with mild cortical compression.

Methods

The present study used short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to evaluate motor cortex excitability in 16 chronic subdural hematoma (CSDH) patients with memory impairment and compared the data with those of 16 healthy controls.

Results

SAI was reduced in patients compared with controls (99 ± 14 vs. 47 ± 11% of the test size; p < 0.0001, unpaired t-test). CSDH patients tended to have a high resting motor threshold and less pronounced SICI and ICF than controls, but these differences were not significant. Treatment of hematoma improved memory impairment and SAI in CSDH patients with wide individual variations that ranged from an increase of 74% to 17% of test size.

Conclusion

These findings suggest that measuring SAI may provide a means of probing the integrity of cortical cholinergic networks in a compressed human brain.     

Prevalence and risk factors for cerebrovascular disease in community-dwelling Latinos

Objectives

Surveys on stroke prevalence may provide valuable information for planning of healthcare services. Few such studies have been conducted in Latinos and none have been performed in Los Angeles, a County that contains the largest population of Latinos in the United States. We sought to assess the prevalence of self-reported stroke in a population-based sample of community-dwelling Latinos in Los Angeles.

Patients and methods

The group comprised of self-identified Latinos aged 40 years and older from six census tracts in Los Angeles participating in a population-based cross-sectional study of ocular disease in Latinos, The Los Angeles Latino Eye Study (LALES). The prevalence of stroke and its association with demographic, biological and behavioral risk factors was determined. Univariate and multiple stepwise logistic regression models were used to calculate odds ratios (ORs).

Results

The prevalence of self-reported stroke in 6954 community-dwelling Latinos in Los Angeles was 3.3%. Stroke prevalence increased with age (1.4% age 40–50, 3.3% age 50–65, 7.1% age >65), history of hypertension (OR 2.6, p < 0.001), heart disease (OR 4.8, p < 0.001) and diabetic retinopathy (OR 2.1, p = 0.01).

Conclusions

Renewed efforts directed at early identification and treatment of hypertension and heart disease within the Latino community will mitigate the burden of stroke.     

Female gender but not cigarette smoking delays the onset of Parkinson's disease

Objective

Cigarette smoking has been proposed as a protective factor against Parkinson's disease (PD); however it is not known whether smoking also delays its onset.

Methods

We conducted a long-term study of 247 patients with idiopathic PD to determine whether smoking and other factors influence its onset and development.

Results

The mean age at disease onset was 57 ± 9 years. In smokers, the intensity and age at which exposure occurred did not modify the beginning of symptoms. Only female gender (p = 0.005) and low educational level (p = 0.03) showed a statistical association in the multivariate analysis with a delayed onset of symptoms.

Conclusion

Our results suggest that females have a delayed onset of symptoms, possibly related to the gonadotropin profile of our population upon the nigrostriatal dopaminergic system. The effect of low educational level may be related to a delayed diagnosis, rather than a true delay of disease onset. This report suggests an influence of gender on the onset of Parkinson's disease.     

Topography of maturational changes in EEG burst spectral power of the preterm infant with a normal follow-up at 2years of age

Objective

To quantify the electroencephalography (EEG) burst frequency spectrum of preterm infants by automated analysis and to describe the topography of maturational change in spectral parameters.

Methods

Eighteen preterm infants <32 weeks gestation and normal neurological follow-up at 2 years underwent weekly 4-h EEG recordings (10–20 system). The recordings (n = 77) represent a large variability in postmenstrual age (PMA, 28–36 weeks). We applied an automated burst detection algorithm and performed spectral analysis. The frequency spectrum was divided into δ1 (0.5–1 Hz), δ2 (1–4 Hz), θ (4–8 Hz), α (8–13 Hz) and β (13–30 Hz) bands. Spectral parameters were evaluated as a function of PMA by regression analysis. Results were interpolated and topographically visualised.

Results

The majority of spectral parameters show significant change with PMA. Highest correlation is found for δ and θ band. Absolute band powers decrease with increasing PMA, while relative α and β powers increase. Maturational change is largest in frontal and temporal region.

Conclusions

Topographic distribution of maturational changes in spectral parameters corresponds with studies showing ongoing gyration and postnatal white matter maturation in frontal and temporal lobes.

Significance

Computer analysis of EEG may allow objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.     

Factors affecting the diagnostic delay in amyotrophic lateral sclerosis

Background

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy).

Objective

To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it.

Methods

We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007.

Results

The median time from onset to diagnosis was 11 months (range: 6–21) for the whole ALS cohort, 10 months (range: 6–15) in bulbar-onset (n = 65) and 12 months (range: 7–23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75–24.25] vs ALS, n = 179, median delay, 9 months [6–15.25], p < 0.001).

Conclusions

The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis.     

Associations of cigarette smoking with intracranial atherosclerosis in the patients with acute ischemic stroke

Background

Although cigarette smoking has been established as an important risk factor for stroke, the effect on the atherosclerotic stenosis, which are based on observational studies, have been controversial. We set out to examine the differences in the risk factors between smokers and nonsmokers and to investigate the association of cigarette smoking with cerebral arterial stenosis.

Methods

A total of 989 consecutive patients with acute noncardioembolic ischemic stroke were prospectively enrolled from June 2004 to January 2010. The risk factor profiles were compared between smokers and nonsmokers. We analyzed the degree of stenosis in all MRA, and evaluated influencing factors in the patients with intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) who were randomly matched by age and sex.

Results

There were differences in the distribution of risk factors between the 467 (70.0%) nonsmokers and the 215 (30.0%) smokers. Nonsmokers were older (71.7 ± 11.0 versus 61.7 ± 12.0, p < 0.001) and had a higher frequency of hypertension than smokers had (75.4% versus 64.0%, p = 0.002). When smokers and nonsmokers were age- and sex-matched, smoking was more prevalent in patients with ICAS than with ECAS (32.9% versus 28.2%). Conditional regression analysis revealed that smoking and hypertension increased the odds of ICAS [smoking, odds ratio (OR): 1.83, p = 0.026; hypertension, OR: 1.84, p = 0.01], whereas hyperlipidemia increased the odds of ECAS (OR: 1.87, p = 0.034).

Conclusion

The distributions of the major risk factors for ischemic stroke were different between smokers and nonsmokers. Cigarette smoking may be more associated with ICAS than with ECAS after adjusting for potential risk factors.